Objective: To test the hypothesis that early stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiac function. Methods: Following 2 wks of rapid ventricular pacing, in 9 anesthetized canines, cardiac and right atrial neuronal function were evaluated in situ in response to enhanced cardiac sensory inputs, stimulation of extracardiac autonomic efferent neuronal inputs and close coronary arterial administration of neurochemicals that included nicotine. Right atrial neuronal intracellular electrophysiological properties were then evaluated in vitro in response to synaptic activation and nicotine. Intrinsic cardiac nicotine sensitive neuronally induced cardiac responses were also evaluated in 8 sham-operated, unpaced animals. Results: Two weeks of rapid ventricular pacing reduced the cardiac index by 54%. Intrinsic cardiac neurons of paced hearts maintained their cardiac mechano- and chemo-sensory transduction properties in vivo. They also responded normally to sympathetic and parasympathetic preganglionic efferent neuronal inputs, as well as to locally administered - or -adrenergic agonists or angiotensin II. The dose of nicotine needed to modify intrinsic cardiac neurons was 50 times greater in failure compared to normal preparations. That dose failed to alter monitored cardiovascular indices in failing preparations. Phasic and accommodating neurons identified in vitro displayed altered intracellular membrane properties compared to control, including decreased membrane resistance, indicative of reduced excitability. Conclusions: Early stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiodynamics. While maintaining its capacity to transduce cardiac mechano- and chemosensory inputs, as well as inputs from extracardiac autonomic efferent neurons, intrinsic cardiac nicotine sensitive local circuit neurons differentially remodel such that their capacity to influence cardiodynamics becomes obtunded.